Final analysis of the phase 3 CheckMate 9ER trial demonstrates that a combination therapy of nivolumab and cabozantinib significantly improves progression-free survival, overall survival, and objective response rates in patients with previously untreated advanced renal cell carcinoma, according to research published in Annals of Oncology.
The trial, involving 651 patients with advanced RCC, randomized participants to receive either first-line nivolumab plus cabozantinib or sunitinib. Results, with a median follow-up of 5.6 years, showed a hazard ratio of 0.58 favoring the nivolumab and cabozantinib combination in terms of progression-free survival, representing a 42% reduction in risk. Median progression-free survival reached 16.4 months for the combination therapy compared to 8.3 months for sunitinib, with 60-month progression-free survival rates of 13.6% versus 3.6%, respectively.
Overall survival also favored the nivolumab plus cabozantinib arm, with a hazard ratio of 0.79. Median overall survival was 46.5 months with the combination, compared to 35.5 months with sunitinib. At 60 months, overall survival rates were 40.9% for the nivolumab and cabozantinib group and 35.4% for the sunitinib group.
The objective response rate was substantially higher with the combination therapy, reaching 55.7% compared to 27.4% with sunitinib. Complete response rates were 13.9% for nivolumab plus cabozantinib and 4.6% for sunitinib. The probability of maintaining a response through 60 months was 22.0% with the combination therapy versus 10.0% with sunitinib.
Treatment-related adverse events occurred in 97.5% of patients receiving nivolumab plus cabozantinib, with grade 3-4 events reported in 67.8%. This compares to 93.1% of patients receiving sunitinib, with grade 3-4 events in 55.0%. Researchers noted that no new deaths attributable to study drug toxicity occurred since the 32.9-month median follow-up reported in a prior analysis.
The CheckMate 9ER trial (NCT03141177) included patients with advanced RCC who had a clear cell component, a common subtype of the disease. The study evaluated the efficacy and safety of the combination therapy as a first-line treatment option, setting a new standard of care for this patient population.
